Escitalopram for the Prevention of PEGASYS-associated Depression in Hepatitis C Virus-infected Patients (CIPPAD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M. Schaefer, MD, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT00136318
First received: August 26, 2005
Last updated: March 20, 2013
Last verified: March 2013
  Purpose

Primary end points

  • incidence of depression defined as a Montgomery Asberg Depression Scale Score (MADRS) of 13 or higher during antiviral therapy (up to 48 weeks, depending on genotype)
  • effect of an antidepressive pre-treatment over two weeks and a continuously concomitant treatment with Escitalopram (S-citalopram) on frequency and severity of depression in patients with chronic hepatitis C (HCV) treated with Peg-interferon alfa-2a (PEGASYS) and ribavirin, measured by the Montgomery Asberg Depression Scale

Secondary end points

  • time to depression defined as a MADRS score of 13 or higher
  • incidence of major depression defined by Diagnostic and Statistical Manual IV (DSM-IV) criteria
  • severe depression according to MADRS scale (score 25 or higher)
  • Health related quality of life (HRQOL) measured by the Short Form 36 (SF-36)
  • sustained virologic response
  • tolerability
  • safety
  • changes/group differences in other psychiatric depression scales (Hamilton Depression Rating Scale, Beck Depression Inventory)

Other investigations:

  • cognitive function, anxiety (word fluency test, trail making test part A and B, othe scales)
  • Predictive parameters for patients especially gaining from an antidepressive therapy (e.g. age, gender, weight, height, alanine aminotransferase (ALAT) quotient defined as median ALAT values before treatment divided by the upper standard value, HCV-RNA serum concentration level of fibrosis in liver histology, baseline values of the different psychometric scales)
  • alanine aminotransferase (ALAT), aspartate transaminase (ASAT), thyrotrophin (TSH)
  • biomarkers (genetic parameters, cytokines,...)

Condition Intervention Phase
Depression
Drug: Escitalopram
Drug: Placebo
Drug: Peginterferon alfa-2a
Drug: Ribavirin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Efficacy and Tolerability of Escitalopram for the Prevention of Pegylated Interferon Alfa Associated Depression in Patients With Chronic Hepatitis C Infection: a Randomized Controlled Trial.

Resource links provided by NLM:


Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • Montgomery Asberg Depression Scale (MADRS) With a Score of 13 or Higher [ Time Frame: 50 weeks for genotypes 1 or 4 and 26 weeks for patients with genotype 2 or 3 ] [ Designated as safety issue: No ]
    Clinically relevant depression (MADRS score of 13 or higher) during antiviral treatment presented as "percentage of participants" with "MADRS scores > 13" (entire time period: from starting study medication until end of antiviral treatment = 48 weeks in patients with genotype 1 or 4 and 24 weeks for patients with genotype 2 or 3)


Secondary Outcome Measures:
  • Proportion of Patients Without Depression (Defined as a MADRS Score of 13 or Higher) [ Time Frame: Patients free of depression during 24 or 48 weeks of antiviral therapy ] [ Designated as safety issue: No ]
    Number of patients who did not develop at any time of antiviral treatment (up to 48 weeks) a MADRS score of 13 or more as a sign of clinically relevant depression

  • Incidence of Major Depression Defined by Diagnostic and Statistical Manual IV (DSM-IV) Criteria [ Time Frame: major depression during 24 or 48 weeks of antiviral therapy ] [ Designated as safety issue: No ]
  • Severe Depression Defined as a MADRS Score of 25 or Higher [ Time Frame: severe depression during 24 or 48 weeks of antiviral therapy ] [ Designated as safety issue: No ]
  • Health Related Quality of Life (HRQOL) Measured by the Short Form 36 (SF-36) [ Time Frame: assessed 2,4,12,24 and 48 weeks of antiviral treatment ] [ Designated as safety issue: No ]
  • Sustained Virologic Response [ Time Frame: assessed 24 weeks after end of antiviral treatment ] [ Designated as safety issue: No ]
    (negative Polymerase Chain Reaction (PCR) 6 months after the end of antiviral treatment)

  • Tolerability [ Time Frame: assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment ] [ Designated as safety issue: Yes ]
  • Safety [ Time Frame: assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment ] [ Designated as safety issue: Yes ]

Enrollment: 208
Study Start Date: January 2004
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Escitalopram
After the preobservation period,patients received escitalopram, 10 mg per day. During treatment period, all patients began receiving antiviral therapy with PEG-interferon plus ribavirin with continuous concomitant administration of escitalopram.
Drug: Escitalopram Drug: Peginterferon alfa-2a
Patients with HCV genotype 1 or 4 received treatment for 48 weeks with PEGinterferon-alfa2a, 180 mcg weekly. Patients with genotype 2 or 3 received PEGinterferon-alfa2a, 180 mcg weekly.
Other Names:
  • PEG-IFN alfa-2a
  • Pegasys
Drug: Ribavirin
Patients with HCV genotype 1 or 4 received treatment for 48 weeks with ribavirin, 1000 mg per day (body weight 75 kg) or 1200 mg per day (body weight, 75 kg). Patients with HCV genotype 2 or 3 received ribavirin, 800 mg per day for 24 weeks.
Other Name: ribavirin
Placebo Comparator: Placebo
After the preobservation period, patients received placebo. After 2 weeks of antidepressant pretreatment, all patients began receiving antiviral therapy with PEG-interferon plus ribavirin with continuous concomitant administration of placebo.
Drug: Placebo Drug: Peginterferon alfa-2a
Patients with HCV genotype 1 or 4 received treatment for 48 weeks with PEGinterferon-alfa2a, 180 mcg weekly. Patients with genotype 2 or 3 received PEGinterferon-alfa2a, 180 mcg weekly.
Other Names:
  • PEG-IFN alfa-2a
  • Pegasys
Drug: Ribavirin
Patients with HCV genotype 1 or 4 received treatment for 48 weeks with ribavirin, 1000 mg per day (body weight 75 kg) or 1200 mg per day (body weight, 75 kg). Patients with HCV genotype 2 or 3 received ribavirin, 800 mg per day for 24 weeks.
Other Name: ribavirin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic hepatitis C infection defined as positive anti-HCV antibodies and serum HCV-RNA >1000 IU/ml, naive to antiviral treatment
  • age >18 years

Exclusion Criteria:

  • Antidepressive treatment within the last 3 years
  • Psychiatric diseases including major depressive disorders in past medical history
  • Active substance abuse during the last 12 months
  • Pregnancy, lactation, wish to become pregnant
  • Hepatitis B (HBV)/HIV-coinfection
  • Decompensated liver disease, hepatocellular carcinoma, history of bleeding esophageal varices
  • Neutropenia (<1500/ul), thrombocytopenia (<70/nl), anemia (<12g/dl in females, <13g/dl in males)
  • History of autoimmune disease
  • History of organ transplantation, concomitant liver disease, severe cardiopulmonary disease, hemolytic anemia, malignant disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00136318

Locations
Germany
Department of Gastroenterolgy and Rheumatology, Sektion Hepatology
Leipzig, Germany, 04103
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
Study Chair: Thomas Berg, Prof. Dr. Charité
Study Chair: Martin Schaefer, Prof. Dr. Charité Berlin
  More Information

No publications provided by Charite University, Berlin, Germany

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M. Schaefer, MD, Martin Schaefer, MD, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT00136318     History of Changes
Other Study ID Numbers: ML18075
Study First Received: August 26, 2005
Results First Received: October 25, 2012
Last Updated: March 20, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:
Pegasys-Induced depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Behavioral Symptoms
Mood Disorders
Mental Disorders
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Dexetimide
Citalopram
Interferon-alpha
Interferons
Ribavirin
Peginterferon alfa-2a
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Parasympatholytics

ClinicalTrials.gov processed this record on September 14, 2014